A new technique has been developed for analyzing DNA for modifications induced by carcinogens and mutagens. The assay advocates a novel approach combining the basic idea of postlabeling the enzymatically digested DNA with a fluorophore and fluorescence detection. Development of He-Cd laser induced fluorescence detection in combination with microbore high performance liquid chromatography has offered a sub-femtomol limit of detection for real-time analysis of dansylated nucleotides. Further improvement in the performance of the assay system as well as application to emerging biological problems requiring highly sensitive detection of DNA modifications are the general objective of the proposed application. The specific aims are: 1) to introduce capillary electrophoresis with laser- induced fluorescence detection as an instrumental method for analysis of the postlabeled nucleotides, 2) to extend the current in vitro DNA damage analysis to in vivo study using well-suited carcinoma cell lines and white blood cells from cancer patients exposed to fluoropyrimidines and platinated drugs.